PROJECT SUMMARY/ABSTRACT A growing body of evidence suggests that persons who misuse opioids and/or develop opioid use disorders are at high risk for transitioning to heroin use, in part because heroin has become more accessible and far less expensive than prescription opioids in many US settings. It is hypothesized that the regional price, purity, and type of heroin available are structural factors that may predict heroin initiation. Further elucidating the complex pathways and mechanisms that link prescription opioid receipt, the development of opioid use disorders, and possible transitions into heroin use is essential to prevent heroin initiation among high-risk populations and reduce overdose mortality in the United States. U.S. military veterans represent a particularly high-risk population, as the impact of military service and its aftermath makes some military personnel and veterans particularly vulnerable to opioid use disorders. It is poorly understood whether opioid prescribing practices within the VA play a role in veterans? risk for initiating heroin use. Heroin initiation among military veterans is particularly troubling because of the additional risks associated with heroin use, including contaminants, injection-associated infections, and vascular disease. To explore this critical public health problem, we plan to examine risk factors for heroin initiation among veterans participating in the Veterans Aging Cohort Study (VACS), a multi-site national study of veterans in primary care. We will use the site of enrollment to link the VACS data to the System to Retrieve Information from Drug Evidence (STRIDE), a publicly available database including the price, purity, and availability of illicit drugs across the United States. The proposed study will address the following aims: Aim 1: to determine whether there exists a dose-response relationship between opioid prescription regimens (including opioid type, dose, and duration) and the greater likelihood of heroin initiation among VACS participants; Aim 2: to examine whether the risk of heroin initiation among VACS participants varies by local heroin market dynamics (price, availability and purity), independent of individual-level risk factors. Improved characterization of medical, behavioral and structural risk factors for heroin initiation is essential to reducing heroin-related morbidity and mortality among veterans and other high-risk populations. Determining whether particular prescribing patterns are associated with heroin initiation could be of great clinical significance at the VA and elsewhere. Additionally, understanding the impact of the local heroin markets on heroin initiation will allow for the development of more comprehensive, regionally-specific intervention strategies.